title: Selective anticancer agents suppress aging in Drosophila.
abstract: Mutations of the PI3K, TOR, iNOS, and NF-κB genes increase lifespan of model organisms and reduce the risk of some aging-associated diseases. We studied the effects of inhibitors of PI3K (wortmannin), TOR (rapamycin), iNOS (1400W), NF-κB (pyrrolidin dithiocarbamate and QNZ), and the combined effects of inhibitors: PI3K (wortmannin) and TOR (rapamycin), NF-κB (pyrrolidin dithiocarbamates) and PI3K (wortmannin), NF-κB (pyrrolidine dithiocarbamates) and TOR (rapamycin) on Drosophila melanogaster lifespan and quality of life (locomotor activity and fertility). Our data demonstrate that pharmacological inhibition of PI3K, TOR, NF-κB, and iNOS increases lifespan of Drosophila without decreasing quality of life. The greatest lifespan expanding effect was achieved by a combination of rapamycin (5 μM) and wortmannin (5 μM) (by 23.4%). The bioinformatic analysis (KEGG, REACTOME.PATH, DOLite, and GO.BP) showed the greatest aging-suppressor activity of rapamycin, consistent with experimental data.
authors.affiliation: Institute of Biology, Komi Science Center, Russian Academy of Sciences, Syktyvkar, 167982, Russia.
authors.forename: Anton
authors.initials: A
authors.lastname: Danilov
authors.forename: Mikhail
authors.initials: M
authors.lastname: Shaposhnikov
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Plyusnina
authors.forename: Valeria
authors.initials: V
authors.lastname: Kogan
authors.forename: Peter
authors.initials: P
authors.lastname: Fedichev
authors.forename: Alexey
authors.initials: A
authors.lastname: Moskalev
mesh_terms: D000375:Aging / Q000187:drug effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004331:Drosophila melanogaster; D005260:Female; D008297:Male; D009154:Mutation; D012737:Sex Factors; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D020123:Sirolimus